Synthesis, biological evaluation and structural determination of beta-aminoacyl-containing cyclic hydrazine derivatives as dipeptidyl peptidase IV (DPP-IV) inhibitors.

Abstract

Inhibitors of dipeptidyl peptidase IV (DPP-IV) have been shown to be effective treatments for type 2 diabetes. A series of beta-aminoacyl-containing cyclic hydrazine derivatives were synthesized and evaluated as DPP-IV inhibitors. One member of this series, (R)-3-amino-1-(2-benzoyl-1,2-diazepan-1-yl)-4-(2,4,5-trifluorophenyl)butan-1-one (10f), showed potent in vitro activity, good selectivity and in vivo efficacy in mouse models. Also, the binding mode of compound 10f was determined by X-ray crystallography.

• Authors: Jin Hee Ahn, Mi Sik Shin, Mi Ae Jun, Sun Ho Jung, Seung Kyu Kang, Kwang Rok Kim, Sang Dal Rhee, Nam Sook Kang, Sun Young Kim, Sang-Kwon Sohn, Sung Gyu Kim, Mi Sun Jin, Jie Oh Lee, Hyae Gyeong Cheon, Sung Soo Kim
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 17 Issue 9 Pg. 2622-8 (May 01 2007) ISSN: 0960-894X [Print] England
• PMID: 17331715 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dipeptidyl-Peptidase IV Inhibitors
• Enzyme Inhibitors
• Hydrazines
• hydrazine
• Glucagon-Like Peptide 1

Topics

• Animals
• Chemistry, Pharmaceutical (methods)
• Crystallography, X-Ray
• Dipeptidyl-Peptidase IV Inhibitors
• Drug Design
• Enzyme Inhibitors (chemical synthesis, pharmacology)
• Glucagon-Like Peptide 1 (metabolism)
• Hydrazines (chemical synthesis, pharmacology)
• Inhibitory Concentration 50
• Kinetics
• Mice
• Mice, Inbred C57BL
• Models, Chemical
• Molecular Conformation
• Protein Structure, Tertiary